アンギオテンシン活性化機構を標的とする大腸癌肝転移治療戦略の確立

2010 年度 研究成果報告書

• 研究課題/領域番号: 20590349
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 人体病理学
• 研究機関: 奈良県立医科大学
• 研究代表者: 國安 弘基 奈良県立医科大学, 医学部, 教授 (00253055)
• 連携研究者: 傳田 阿由美 奈良県立医科大学, 医学部, 講師 (90110858) ; 笹平 智則 奈良県立医科大学, 医学部, 助教 (90405374) ; 大森 斉 奈良県立医科大学, 医学部, 博士研究員 (80213875) ; 藤井 澄 奈良県立医科大学, 医学部, 博士研究員 (60284189) ; バワール ウジャール 奈良県立医科大学, 医学部, 博士研究員 (50433339)
• 研究期間 (年度): 2008 – 2010
• キーワード: 消化器 / 唾液腺

研究概要

本課題ではアンギオテンシン系の腫瘍における作用を総合的に検討した。高血糖は大腸癌細胞にレニン発現を誘導し、キマーゼとともにアンギオテンシンを活性化し、肝転移を促進した。アンギオテンシン分解産物のアンギオテンシン1-7受容体であるMAS1の発現は乳癌特にスキルス癌で顕著に低下しstage、リンパ節転移、HER2発現と逆相関した。MAS1は乳癌における新たな癌抑制遺伝子と考えられた。このように、癌におけるアンギオテンシンの役割に応じた標的治療が有効であると考えられる。

研究成果

• [雑誌論文] Non-histone nuclear factor HMGB1 as a target in colorectal cancer. (2011)
  • 著者名/発表者名: Ohmori H, Luo Y, Kuniyasu H
  • 雑誌名: Expert Opin Ther Tar 15(2) ページ: 183-193
• [雑誌論文] Downregulation of runt-related transcription factor 3 (RUNX3) associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland. (2011)
  • 著者名/発表者名: Sasahira T, Kurihara M, Yamamoto K, Bhawal UK, Kirita T, Kuniyasu H
  • 雑誌名: Cancer Sci 102(2) ページ: 492-497
• [雑誌論文] In vitro enhanced differentiation of neural networks in ES gut-like organ from mouse ES cells by a 5-HT4-receptor activation. (2011)
  • 著者名/発表者名: Takaki M, Misawa H, Matsuyoshi, H, Kawahara I, Goto K, Zhang GX, Obata K,Kuniyasu H
  • 雑誌名: Biochem Biophys Res Commun 406(4) ページ: 529-533
• [雑誌論文] HMGB1 attenuates anti-metastatic defense of the lymph nodes in colorectal cancer. (2010)
  • 著者名/発表者名: Moriwaka Y, Luo Y, Ohmori H, Fujii K, Tatsumoto N Sasahira T, Kuniyasu H
  • 雑誌名: Pathobiology 77(1) ページ: 17-23
• [雑誌論文] CD10 enhances metastasis of colorectal cancer by abrogating the antitumoral effect of methionine-enkephalin in the liver. (2010)
  • 著者名/発表者名: Kuniyasu H : Luo Y, Fujii K, Sasahira T, Moriwaka Y, Tatsumoto N, Sasaki T, Yamashita Y, Ohmori H.
  • 雑誌名: Gut 59(3)(On line publication Oct 14, 2009) ページ: 348-56
• [雑誌論文] HMGB1 attenuates anti-metastatic defense of the liver in colorectal cancer. (2010)
  • 著者名/発表者名: Luo Y, Ohmori H, Fujii K, Moriwaka Y, Sasahira T, Kurihara M, Tatsumoto N, Sasaki T, Yamashita Y, Kuniyasu H
  • 雑誌名: Eur J Cancer 46(4) ページ: 791-799
• [雑誌論文] A 5-HT4-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult. (2010)
  • 著者名/発表者名: Matsuyoshi H, Kuniyasu H, Okumura M, Misawa H, Katsui R, Zhang GX, Obata K, Takaki M
  • 雑誌名: Neurogastroenterol Motil 22(7) ページ: 806-814
• [雑誌論文] Dietary linoleic acid and glucose enhances azoxymethane-induced colon cancer and the metastasis through the expression of high mobility group box 1. (2010)
  • 著者名/発表者名: Ohmori H, Luo Y, Fujii K, Sasahira T, Shimomoto T, Denda A, Kuniyasu H
  • 雑誌名: Pathobiology 77(4) ページ: 210-217
• [雑誌論文] MIA dependent angiogenesis and lymphangiogenesis are closely associated with progression, nodal metastasis and poor prognosis in tongue squamous cell carcinoma. (2010)
  • 著者名/発表者名: Sasahira T, Kirita T, Kurihara M, Yamamoto K, Bhawal UK, Bosserhoff AK, Kuniyasu H
  • 雑誌名: Eur J Cancer 46 ページ: 2285-2294
• [雑誌論文] Determinants of the epithelial-muscle axis on embryonic stem cell-derived gut-like structures. (2010)
  • 著者名/発表者名: Luo Y, Takaki M, Misawa H,Matsuyoshi H, Sasahira T, Chihara Y, Fujii K, Ohmori H, Kuniyasu H
  • 雑誌名: Pathobiology 77(5) ページ: 253-259
• [雑誌論文] A case of gastric cancer with non-islet cell tumor hypoglycemia detected by insulin-like growth factor II. (2010)
  • 著者名/発表者名: Maruyama H, Tatsumi M, Kitayama H, Enomoto Y, Kuniyasu H, Uematsu K, Fukuda I, Kameya T, Konishi Y.
  • 雑誌名: Pathol Int 60(8) ページ: 595-597
• [雑誌論文] The plasticity of the defecation reflex pathway in the enteric nervous system of guinea pigs. (2009)
  • 著者名/発表者名: Katsui R, Kuniyasu H, Matsuyoshi H, Fujii H, Nakajima Y, Takaki M.
  • 雑誌名: J Smooth Muscle Res 45(1) ページ: 1-13
• [雑誌論文] Reg IV enhances peritoneal metastasis in gastric carcinomas. (2009)
  • 著者名/発表者名: Kuniyasu H : Oue N, Sasahira T, Moriwaka Y, Shimomoto T, Fujii K, Ohmori H, Yasui W
  • 雑誌名: Cell Prolif 42(1) ページ: 110-121
• [雑誌論文] Co-treatment with deoxycholic acid and azoxymethane accelerates the secretion of HMGB1 in IEC6 intestinal epithelial cells. (2009)
  • 著者名/発表者名: Fujii K, Luo Y, Sasahira T, Denda A, Ohmori H, Kuniyasu H
  • 雑誌名: Cell Prolif 42(5) ページ: 701-709
• [雑誌論文] Methionine-enkephalin secreted by human colorectal cancer cells suppresses T lymphocytes. (2009)
  • 著者名/発表者名: Ohmori H, Fujii K, Sasahira T, Luo Y, Isobe M, Tatsumoto N, Kuniyasu H
  • 雑誌名: Cancer Sci 100(3) ページ: 497-502
• [雑誌論文] Suppression of dendritic cells by HMGB1 is associated with lymph node metastasis of human colon cancer. (2009)
  • 著者名/発表者名: Kusume A, Sasahira T, Luo Y, Isobe M, Nakagawa N, Tatsumoto N, Fujii K, Ohmori H, Kuniyasu H
  • 雑誌名: Pathobiology 76(4) ページ: 155-162
• [雑誌論文] Antisense phosphorothioate oligodeoxynucleic acid for CD10 suppresses liver metastasis of colorectal cancer. (2009)
  • 著者名/発表者名: Luo Y, Fujii K, Ohmori H, Sasahira T, Moriwaka Y, Isobe M, Kuniyasu H
  • 雑誌名: Pathobiology 76(5) ページ: 267-273
• [雑誌論文] The roles of dietary PPAR_Y ligands for metastas in colorectal cancer. (2008)
  • 著者名/発表者名: Kuniyasu H
  • 雑誌名: In PPARs : A Double-Edged Sword in Cancer Therapy?((ed) Panigrahy D.PPAR Res) 2008 ページ: 529720
• [雑誌論文] Loss of 14-3-3 sigma expression and human papillomavirus 16 E6 presence in oral squamous cell carcinoma. (2008)
  • 著者名/発表者名: Bhawal UK, Sugiyama M, Nomura Y, Sawajiri M, Otsubo A, Tsukinoki K, Ikeda M, Kuniyasu H
  • 雑誌名: Arch Otolaryngol Head Neck Surg. 134(10) ページ: 1055-1059
• [雑誌論文] Recurrence of keratocystic odontogenic tumor : clinico- pathological features and immunohistochemical study of the hedgehog signaling pathway. (2008)
  • 著者名/発表者名: Yagyuu T, Kirita T, Sasahira T, Moriwaka Y, Yamamoto K, Kuniyasu H
  • 雑誌名: Pathobiology 75(3) ページ: 171-176
• [雑誌論文] Linoleic acid-induced growth suppression induces quiescent cancer cell nests in nude mice. (2008)
  • 著者名/発表者名: Ohmori H, Sasahira T, Fujii K, Luo Y, Shimomoto T, Kuniyasu H
  • 雑誌名: Pathobiology 75(4) ページ: 226-232
• [雑誌論文] Protection of telomeres protein levels are associated with telomere length in gastric cancer. (2008)
  • 著者名/発表者名: Fujii K, Sasahira T, Moriwaka Y, Oue N, Yasui W, Kuniyasu H
  • 雑誌名: Int J Mol Med 21(5) ページ: 599-604
• [雑誌論文] Plastticity of enteric nerve pathways for the recto-rectal and recto-internal sphincter reflexs in guinea pigs. (2008)
  • 著者名/発表者名: Katsui R, Kojima Y, Kuniyasu H, Shimizu J, Koyama F, Fujii H, Nakajima Y, Takaki M
  • 雑誌名: Am J Physiol Gastrointest Liver Physiol 294(4) ページ: G1084-G1093
• [雑誌論文] Serous borderline tumor of the paratestis. (2008)
  • 著者名/発表者名: Maruyama H, Ohyama N, Hosokawa Y, Momose H, Yamada K, Tsutsumi M, Kuniyasu H, Enomoto Y, Uematsu K, Konishi Y
  • 雑誌名: Pathol Int 58(5) ページ: 311-316
• [雑誌論文] Reg IV is an independent prognostic factor for relapse in patients with clinically localized prostate cancer. (2008)
  • 著者名/発表者名: Ohara S, Oue N, Matsubara A, Mita K. Hasegawa Y, Hayashi T, Usui T, Amatya V, Takeshima Y, Kuniyasu H, Yasui W
  • 雑誌名: Cancer Sci 99(8) ページ: 1570-1577
• [雑誌論文] High mobility group box-1-inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma. (2008)
  • 著者名/発表者名: Sasahira T, Kirita T, Oue N, Bhawal UK, Yamamoto K, Fujii K, Ohmori H, Luo Y, Yasui W, Bosserhoff AK, Kuniyasu H
  • 雑誌名: Cancer Sci 99(9) ページ: 1806-1812
• [雑誌論文] Reg IV expression is associated with cell growth and prognosis of adenoid cystic carcinoma in the salivary gland. (2008)
  • 著者名/発表者名: Sasahira T, Oue N, Kirita T, Luo Y, Bhawal UK, Yasui W, Kuniyasu H
  • 雑誌名: Histopathol 53(6) ページ: 667-675
• [雑誌論文] Evaluation of metastatic potential of prostate cancer.
  • 著者名/発表者名: Chihara Y, Fujimoto K, Hirao Y, Kuniyasu H
  • 雑誌名: Oncol Rev in press
• [雑誌論文] The roles of HMGB1 related angiogenesis and lymphangiogenesis in oral cancer.
  • 著者名/発表者名: Sasahira T, Yamamoto K, Kurihara M, Bhawal UK, Chihara Y, Kirita T, Kuniyasu H
  • 雑誌名: Oncol Rev in press
• [雑誌論文] Basic helix-loop-helix transcription factor DEC1 negatively regulates CyclinD1.
  • 著者名/発表者名: Bhawal UK, Sato F, Arakawa Y, Fujimoto K, Kawamoto T, Tanimoto K, Ito Y, Sasahira T, Sakurai T, Kobayashi M, Kashima I, Kajima H, Kuniyasu H, Abiko Y, Kato Y, Sato S
  • 雑誌名: J Pathol in press
• [雑誌論文] Involvement of HMGB1 and RAGE in IL-1β-induced gingival inflammation.
  • 著者名/発表者名: Ito Y, Bhawal UK, Sasahira T, Toyama T, Sato T, Matsuda D, Kobayashi M, Sugiyama M, Hamada N, Arakawa H, Kuniyasu H
  • 雑誌名: Arch Oral Biol in press
• [雑誌論文] High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer.
  • 著者名/発表者名: Luo Y, Ohmori H, Fujii K, Chihara Y, Maruyama S, Kuniyasu H
  • 雑誌名: Urol Oncol-Semin Ori in press
• [雑誌論文] Anti-angiotensin and hypoglycemic treatments suppress liver metastasis of colon cancer cells.
  • 著者名/発表者名: Luo Y, Ohmori H, Shimomoto T, Fujii K, Kuniyasu H
  • 雑誌名: Pathobiology in press
• [学会発表] HMGB1 affects plasma amino acid profiles in colon carcinogenesis. (2011)
  • 著者名/発表者名: Luo Y, Yoneda J, Ohmori H, Shimbo K, Eto S, Fujii K, Sasahira T, Chihara Y, Kuniyasu H
  • 学会等名: 102nd Annual Meeting of American Association for Cancer Research
  • 発表場所: Florida
  • 年月日: 20110402-20110406
• [学会発表] HMGB1の間葉系幹細胞への影響 (2010)
  • 著者名/発表者名: 國安弘基、羅奕、千原良友、笹平智則、傳田阿由美、大森斉、品川慶、北台靖彦
  • 学会等名: 第25回発癌病理研究会「幹細胞」(国際学会)
  • 発表場所: 松島
  • 年月日: 20100824-20100826
• [学会発表] Expression of MAS1 in breast cancer. (2010)
  • 著者名/発表者名: Luo Y, Chihara Y, Fujii K, Moriwaka Y, Ohmori H, Kuniyasu H
  • 学会等名: 20th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2010-10-31
• [学会発表] MIA induces angiogenesis and lymphangiogenesis. (2010)
  • 著者名/発表者名: 笹平智則, 國安弘基
  • 学会等名: Japan-Korea Urology Research Meeting 2010
  • 発表場所: Kashihara
  • 年月日: 2010-05-22
• [学会発表] Diagnostic indicator of urological cancer based on quantitative DNA methylation analysis. (2010)
  • 著者名/発表者名: 千原良友, 國安弘基
  • 学会等名: Japan-Korea Urology Research Meeting 2010
  • 発表場所: Kashihara
  • 年月日: 2010-05-22
• [学会発表] 大腸癌のアンギオテンシン活性化能は肝転移と相関する (2009)
  • 著者名/発表者名: 大森斉、大家理伸、森若優希子、笹平智則、立本直邦、國安弘基
  • 学会等名: 第20回日本消化器癌発生学会、ミニシンポジウム(5)-3消化器癌の分子基盤:浸潤・転移-3
  • 発表場所: 広島
  • 年月日: 20091126-20091127
• [学会発表] Activation of angiotensin system enhances liver metastasis of human colorectal cancer. (2009)
  • 著者名/発表者名: Kuwai T, Kitadai Y, Luo Y, Sasahira T, Masaki K, Kohno H, Isobe M, Ohmori H, Kuniyasu H
  • 学会等名: 100th Annual Meeting of American Association for Cancer Research
  • 発表場所: Denver
  • 年月日: 20090418-20090422
• [学会発表] Cancer cell necrosis induces tumor growth and metastasis by releasing HMGB1. (2009)
  • 著者名/発表者名: Kitadai Y, Luo Y, Ohmori H, Fujii K, Sasahira T, Chihara Y, Kuniyasu H
  • 学会等名: 101th Annual Meeting of American Association for Cancer Research
  • 発表場所: Washington DC
  • 年月日: 20090417-20090721
• [学会発表] Methionine-enkephalin inhibits liver metastasis of colorectal cancers. (2009)
  • 著者名/発表者名: Luo Y, Moriwaka Y, Fujii K, Ohmori H, Kuniyasu H
  • 学会等名: 19th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2009-10-01
• [学会発表] Angiotensin II expression is associated with liver metastasis of colorectal cancer. (2009)
  • 著者名/発表者名: Luo Y, Isobe M, Fujii K, Ohmori H, Kuniyasu H
  • 学会等名: 19th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2009-10-01
• [学会発表] Receptor for advanced glycation end products (RAGE) is associated with prognosis and angiogenesis in human oral squamous cell carcinoma (OSCC). (2008)
  • 著者名/発表者名: Sasahiar T, Kuniyasu H, Luo Y, Bhawal UK, Yamamoto K, Kirita T
  • 学会等名: 12th International Congress on Oral Cancer
  • 発表場所: Shanghai
  • 年月日: 20080522-20080525
• [学会発表] CD10 reduces inhibitory effect of Metenkephalin in colon cancer. (2008)
  • 著者名/発表者名: Moriwaka Y, Kuwai T, Sasahira T, Ohmori H, Kitadai Y, Kuniyasu H
  • 学会等名: 99th Annual Meeting of American Association for Cancer Research
  • 発表場所: San Diego
  • 年月日: 20080412-20080416
• [学会発表] Activation of angiotensin system enhances liver metastasis of human colorectal cancer. (2008)
  • 著者名/発表者名: Ohya M, Iwatsubo S, Moriwaka Y, Luo Y, Denda A, Ohmori H, Kuniyasu H
  • 学会等名: 18th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2008-11-09
• [学会発表] CD10 abrogates immune disturbance by beta-casomorphin in intestinal mucosa. (2008)
  • 著者名/発表者名: Kaya D, Fukuoka H, Luo Y, Shimomoto T, Sasahira T, Ikeda M, Fujii K, Ohmori H, Kuniyasu H
  • 学会等名: 18th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2008-11-09
• [学会発表] A trans fatty acid, eridic acid enhanses metastasis of colorectal cancer. (2008)
  • 著者名/発表者名: Toyama Y, Nishii R, Sasahira T, Luo Y, Fujii K, Ohmori H, Kuniyasu H
  • 学会等名: 18th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2008-11-09
• [学会発表] CD10 enkephalinase enhances liver metastasis by suppression of Kupffer cell-derived Methionine-enkephalin in human colorectal cancer. (2008)
  • 著者名/発表者名: Luo Y,, Shimomoto T, Tatsumoto N, Fujii K, Kuniyasu H
  • 学会等名: 18th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2008-11-09
• [学会発表] Suppression of dendritic cells by HMGB1 is associated with lymph node metastasis of human colon cancer. (2008)
  • 著者名/発表者名: Luo Y, Sasahira T, Isobe M, Nakagawa N, Tatsumoto N, Ohmori H, Kuniyasu H
  • 学会等名: 18th International Symposium of Hiroshima Cancer Seminar
  • 発表場所: Hiroshima
  • 年月日: 2008-11-09
• [図書] HMGB1 induces drug resistance in cancer cells.(Current research in cancer 5, 2011)(eds : Sunitha M.)B5 Kerala, India (2011)
  • 著者名/発表者名: Kuniyasu H
  • 出版者: Research Media
• [図書] Recent advances in metastasis of gastrointestinal cancers. B5 Kerala, India (2010)
  • 著者名/発表者名: Kuniyasu H, Kitadai Y
  • 総ページ数: 214
  • 出版者: Transworld Research Network
• [図書] Hyperplastic change of the mucosa adjacent to colorectal carcinomas : a newly recognized cancer-host relationship.(Recent advances in metastasis of gastrointestinal cancers)(eds : Kuniyasu H, Kitadai Y.)A5 India (2010)
  • 著者名/発表者名: Kuniyasu H
  • 総ページ数: 65-85
  • 出版者: Transworld Research Network
• [図書] Angiogenesis and lymphangiogenesis in oral cancer.(Recent advances in metastasis of gastrointestinal cancers)(eds : Kuniyasu H, Kitadai Y.)A5 India (2010)
  • 著者名/発表者名: Sasahira T, Kuniyasu H
  • 総ページ数: 22-40
  • 出版者: Transworld Research Network
• [図書] Diverse roles of linoleic acid on development and progression of colorectal cancer.(Recent advances in metastasis of gastrointestinal cancers)(eds : Kuniyasu H, Kitadai Y.)A5 India (2010)
  • 著者名/発表者名: Luo Y, Kuniyasu H
  • 総ページ数: 87-102
  • 出版者: Transworld Research Network
• [図書] Histological characteristics of the colorectal cancer metastasized to the liver.(Recent advances in metastasis of gastrointestinal cancers)(eds : Kuniyasu H, Kitadai Y.)A5 India (2010)
  • 著者名/発表者名: Ohmori H, Tatsumoto N, Kuniyasu H
  • 総ページ数: 161-173
  • 出版者: Transworld Research Network
• [図書] Peritoneal dissemination of gastric cancer.(Recent advances in metastasis of gastrointestinal cancers)(eds: Kuniyasu H, Kitadai Y.)A5 Kerala, India (2010)
  • 著者名/発表者名: Fujii K, Kuniyasu H
  • 総ページ数: 115-130
  • 出版者: Transworld Research Network
• [図書] RAGE, AGE, and HMGB1-dramatypes of Western diet in colon cancer development.(Current research in cancer 4, 2010)(eds : Sunitha M.)Kerala, India (2010)
  • 著者名/発表者名: Kuniyasu H
  • 出版者: Research Media In press
• [図書] Application of in situ hybridization technique to pathology researches.(Research advances in histopathology 1)(eds : Sunitha M.)B5, Kerala, India (2010)
  • 著者名/発表者名: Kuniyasu H
  • 総ページ数: 1-9
  • 出版者: Research Media
• [図書] Linoleic acid.(Encyclopedia of cancer, 2^<nd> edition)((ed) Schwab M.)Berlin (2009)
  • 著者名/発表者名: Kuniyasu H
  • 総ページ数: 3235
  • 出版者: Springer-Verlag,
• [図書] CD10-a significant determinant of liver metastasis in colon cancer.(Current research in cancer 3, 2009)(eds : Sunitha M.)B5 Kerala, India (2009)
  • 著者名/発表者名: Kuniyasu H
  • 総ページ数: 65-73
  • 出版者: Research Media
• [図書] Application of in situ hybridization technique to pathology researches.(Current Research in Pathology)(eds : Sunitha M.)B5 Kerala, India (2009)
  • 著者名/発表者名: Kuniyasu H
  • 総ページ数: 1-12
  • 出版者: Research Media
• [図書] New angiogenic factors in oral cancer.(Current Research in Cancer 2008)((ed) Sunitha M.)Kerala, India (2008)
  • 著者名/発表者名: Kuniyasu H
  • 総ページ数: 1-11
  • 出版者: Research Media
• [備考] ホームページ等
  • URL: http://www.naramed-u.ac.jp/~molepath/